慢性淋巴细胞白血病疾病进展的基因和表观遗传分析揭示了有限的体细胞进化，并提示其与记忆细胞发育的关系。
Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development.
作者信息
Smith E N, Ghia E M, DeBoever C M, Rassenti L Z, Jepsen K, Yoon K-A, Matsui H, Rozenzhak S, Alakus H, Shepard P J, Dai Y, Khosroheidari M, Bina M, Gunderson K L, Messer K, Muthuswamy L, Hudson T J, Harismendy O, Barrett C L, Jamieson C H M, Carson D A, Kipps T J, Frazer K A
机构信息
1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
1] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [2] Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
出版信息
Blood Cancer J. 2015 Apr 10;5(4):e303. doi: 10.1038/bcj.2015.14.
We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells.
我们使用来自27名患者的系列样本，研究了慢性淋巴细胞白血病（CLL）从惰性形式发展为侵袭性形式的疾病进展过程中发生的遗传和表观遗传变化。对DNA突变的分析将白血病病例分为三类：进化型（26%）、扩增型（26%）和稳定型（47%）。因此，约四分之三的CLL病例几乎没有或没有遗传亚克隆进化。然而，我们在4752个CpG位点发现了疾病进展过程中显著的复发性DNA甲基化变化，这些位点富集于多梳抑制复合物2（PRC2）靶标的附近区域。PRC2靶标附近与疾病进展相关的CpG位点在疾病进展过程中发生的甲基化变化方向，与从初始B细胞到记忆B细胞的正常发育过程中相同。我们的研究表明，CLL进展通常不是通过亚克隆进化发生的，而是某些CpG位点会发生复发性甲基化变化。我们的结果表明，CLL进展可能涉及与正常记忆B细胞生成共有的发育过程。
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